Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy

Goicoechea, Marián; Gómez-Preciado, Francisco; Benito, Silvia; Torrás, Joan; Torrá, Roser; Huerta, Ana; Restrepo, Alvaro; Ugalde, Jessica; Astudillo, Daniela; Agraz, Irene; Lopez-Mendoza, Manuel; Arriba, Gabriel de; Corchete, Elena; Quiroga, Borja; Gutiérrez, Maria Jose; Martin-Conde, Maria Luisa; Lopes, Vanessa; Ramos, Carmela; Méndez, Irene; Cao, Mercedes; Domínguez, Fernándo; Ortíz, Alberto

doi:10.1016/j.nefroe.2022.01.003

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…Six out of 97 presented with a VUS. Regarding the remaining 91 females, variants associated with classic and non-classic phenotypes were similarly distributed (40% and 54%, respectively), which is in line with the literature [ 29 , 30 ]. Missense variants were identified in 84 (87%) females, of which 72% of the variants fell within the classic type, demonstrating that carrying a missense variant does not exclude this associated phenotype.…”

Section: Discussionsupporting

confidence: 89%

The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants

Sánchez-Martínez

Ripoll‐Vera

Lopez-Mendoza

et al. 2023

Orphanet J Rare Dis

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Background Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. Results Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). Conclusions Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.

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Section: Discussionsupporting

confidence: 89%

The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants

Sánchez-Martínez

Ripoll‐Vera

Lopez-Mendoza

et al. 2023

Orphanet J Rare Dis

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“…Tis report describes two unrelated female patients with FD harbouring the same GLA p. Ile270Tr pathogenic variant and the efect of early treatment, not only on symptoms and surrogates, including LVM and GFR, but also on clinical events. Te literature has extensively described this variant in association with the classic Fabry phenotype [11,[16][17][18][19][20][21]. Specifc features of advanced disease, such as cardiac fbrosis or severe renal dysfunction, are hallmarks of irreversible organ damage.…”

Section: Discussionmentioning

confidence: 99%

The Benefits of Early versus Late Therapeutic Intervention in Fabry Disease

Furlano

Ars

Matamala

et al. 2022

Case Reports in Genetics

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Background. Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants of the GLA gene. Heterozygous female patients may show much more variability in clinical manifestations, ranging from asymptomatic to full-blown disease. Because of this heterogeneous clinical picture in women, the diagnosis of FD has typically been delayed for more than a decade, and the optimal time to initiate treatment remains controversial. Case Presentation. Here, we present two unrelated female patients diagnosed with FD harbouring the same pathogenic GLA variant. We discuss the implications of initiating specific therapy at different stages of the disease, with and without organ involvement (early versus late therapeutic intervention). Conclusions. These clinical cases suggest that initiating specific treatment at an earlier age in women with FD may prevent organ involvement and associated clinical events.

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“…4 Enzyme replacement therapy (ERT) with recombinant human α-Gal A for treatment of Fabry's disease is in clinical use since 2001. 23 There are two therapeutic enzymes available for intravenous administration: agalsidase α (Replagal) and agalsidase β (Fabrazyme), 4,19,24 of which only the latter is approved by the US Food and Drug Administration (FDA). 74 Replagal, manufactured by Shire Pharmaceuticals Ireland Limited, Ireland, and marketed by Shire Human Genetic Therapies AB, Sweden (https://www.ema.europa.eu/en/documents/productinformation/replagal-epar-product-information_en.pdf), is produced from human fibroblast cell lines.…”

Section: Enzyme Replacement Therapy For Fabry's Diseasementioning

confidence: 99%

Biopharmaceutical applications of α‐galactosidases

Anisha¹

2022

Biotech and App Biochem

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α‐Galactosidases are exoglycosidases that are active on galactose‐containing side chains in oligosaccharides, polysaccharides, glycolipids, and glycoproteins. α‐Galactosidases are gaining increased interest in human medicine, especially in the enzyme replacement therapy for Fabry's disease. α‐Galactosidases with regioselectivity toward α‐1,3‐linked galactose find application in xenotransplantation and blood group transformation. The use of α‐galactosidases as a therapeutic agent in alleviating the postprandial symptoms of irritable bowel syndrome is much acclaimed. The excellent therapeutic applications of α‐galactosidases have led to an upwelling of worldwide research interventions to identify novel α‐galactosidases with improved catalytic efficiency. In addition to these therapeutic applications, α‐galactosidases also have interesting applications in the industrial sectors like food, feed, probiotics, sugar, and paper pulp. The current review focuses on the diverse therapeutic applications of α‐galactosidases and their prospects.

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Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy

Cited by 4 publications

References 27 publications

The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants

The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants

The Benefits of Early versus Late Therapeutic Intervention in Fabry Disease

Biopharmaceutical applications of α‐galactosidases

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